The field of this invention is the area of antimicrobial agents and methods of treating infections and/or inhibiting microbial growth. Specifically, the present invention relates to inhibition of microbial growth and treating infections, especially those cause by pathogenic bacteria, with artificial metalloporphyrin.
The high incidence of microbial resistance to multiple antibiotics has seriously complicated treatment of infections of both outpatients and patients who have acquired hospital-associated infections. This rise in resistance to multiple antibiotics has made many otherwise very potent and inexpensive antibiotics almost obsolete [Cohen, M. L. (1992) Science, 257, 1050-1055; Neu, H. C. (1992) Science 257, 1064-1073]. Patients infected by multiply resistant bacteria have more severe clinical courses and require prolonged hospital treatments. Costs associated with these hospital acquired infections with resistant bacteria have been estimated to cost between $4 million and $30 billion per year in the United States alone [Haley, R. W. (1986) Managing Hospital Infection Control for Cost Effectiveness, Chicago, Ill., American Hospital Publishing]. Recent emergence of strains of enterococci which are resistant to all available antibiotics and chemotherapeutic agents is a clear reminder that, despite intensive research and production of new antibiotics, there is a real danger that the epidemic of multiple antibiotic resistance might not be stopped [Spera and Farber (1992) J.A.M.A. 268, 2563-2564]. Respiratory infections are a particularly serious problem due to their high incidence and alarmingly high mortality rates. Approximately 300,000 nosocomial lower respiratory infections occur each year in the United States, with mortality rates ranging between 20% and 50% [Pennington, J. E. in Harrison's Principles of Internal Medicine, 13th edition, K. I. Isselbacher et al., eds.].
The development of new antibiotics is a very costly endeavor with which, together with the lengthy process to obtain regulatory approval, is causing at least some pharmaceutical companies to abandon work in this area [Reich, M. R. (1987) Health Pol. 8,39-57; Slater, A. J. (1989) Trans. Royal Soc. Trop. Med. Hyg. 83, 45-48]. Thus, there is an urgent need in the art for the identification of new bacterial targets for antibiotic action and for the discovery of new antibacterial compounds that will foil bacterial resistance mechanisms.